Summary of Work: Proposed studies build upon an existing longitudinal study of respiratory health in relation to ambient air pollution conducted at USC. Approximately 3600 children from 12 communities in Southern California chosen to maximize contrast in exposure to ozone, particles, acids and nitrogen oxides are being followed over a 7-year period. We plan to examine genetic susceptibility to asthma and other respiratory outcomes and test for gene-environment interaction and will collect buccal cell samples to archive DNA on all children in the study. We are pilot testing protocols for collection. DNA samples will be used to test for associations between asthma and candidate genes in a nested case-control design. The study offers the advantage of sampling a representative control group from among children in the cohort without asthma. There are currently a number of candidate genes to test but we anticipate that by the time the collection is complete the list will evolve based on results from genome wide searches in asthma families. Because interpretation of results of population association studies of candidate genes is always limited by the possibility of population stratification, we are interested in collecting buccal cell samples from parents and siblings of children with asthma -- parents and siblings. We will pilot test these family collections in the coming year. We also plan in the next year to pilot test collection of DNA samples in a companion study of health effects of air pollution in Mexico City which will expand our sample of Hispanic children and provide a location with higher ozone exposure. Identification of susceptibility genes may help to clarify weak associations between pollutants and disease, improve the understanding of pathogenesis, prevention, and even be relevant to therapeutics.